Selected patients with medically refractory autoimmune disease (MRAID) have a uniformly dismal prognosis. High dose chemotherapy followed by autologous stem cell transplant (AutoSCT) has induced transient stabilization of disease but has been associated with significant morbidity and mortality and ultimate progression of disease. Recently, reduced intensity (RI) conditioning followed by allogeneic stem cell transplant (AIIoSCT) has resulted in mixed or complete donor chimerism in both malignant and other nonmalignant diseases. We hypothesize that RI chemoimmunotherapy followed by AlloSCT + donor lymphocyte infusion (DLI) will be well tolerated and result in mixed or complete donor chirnerism and stabilization of disease in patients with MRAID. The primary specific aims include: 1) to determine the toxicity of RI conditioning with fludarabine, busulfan and alemtuzumab (FBA) followed by AIIoSCT; 2) to quantitate percent mixed and complete donor chimerism following FBA and AIIoSCT + DLI; 3) to measure immune reconstitution following FBA and AIIoSCT _+DLI; 4) to determine the probability of disease progression and survival following FBA and AlloSCT + DLI; and 5) to determine the incidence and changes of preexisting maternal-fetal derived microchimerism (<1%). The secondary aims include: 6) the toxicity and response rate of DLI following induction of donor tolerance; 7) to measure the changes in humoral and cellular autoimmune markers following FBA and AlloSCT + DLI; 8) to estimate the probability of acute and chronic GVHD following FBA, AIIoSCT and FK506 and mycophenolate mofetil (MMF) prophylaxis; and 9) to determine the quality of life before and after FBA and AlloSCT. The methods to determine the probability of disease progression, survival and acute and chronic GVHD will use the product-limit method (Kaplan Meier); Whole Blood, T-cell and NK chimerism will be performed by flow cytometry sorting and chimerism by short tandem repeats (STR), kinetic PCR and/or variable number tandem repeats (VNTR); immune reconstitution by flow cytometry, TREC, alpha/beta T-cell receptor CDR3 length distribution (spectratyping); and quality of life by standard evaluations. The results of this novel and innovative strategy (if successful and safe) could offer a new strategy for the treatment of patients with very poor risk autoimmune diseases and form the basis for a future multicenter prospective and randomized study comparing this approach to standard of care.